MedNess: bite-size biopharma and medtech news

Keytruda gets green light from the FDA in high-risk, early stage TNBC
On 26^th July, the US FDA has approved Merck’s Keytruda (pembrolizumab) in combination with chemotherapy as neoadjuvant therapy followed by adjuvant monotherapy in high-risk, early-stage triple-negative breast cancer (TNBC) patients. FDA also converted accelerated approval in PD-L1+, 1L TNBC to regular approval. The approval is based on the pivotal Phase 3 KEYNOTE-522 study.
Background: Early stage TNBC is an area of high unmet need with poorer outcomes and survival. High-risk early stage TNBC is also associated with higher recurrence rates within 5 years with 30-40% recurring after neoadjuvant therapy and surgery. Chemotherapy is the only standard of care for high-risk early stage TNBC patients.
Details: Phase 3 KEYNOTE-522 is evaluating Keytruda as neoadjuvant therapy in combination with chemotherapy (carboplatin + paclitaxel followed by doxorubicin/epirubicin + cyclophosphamide) and continued as monotherapy adjuvant treatment vs. neoadjuvant chemotherapy followed by adjuvant placebo in 1,174 high-risk, previously untreated stage II/III TNBC patients.
In mid-July, Merck had announced that Keytruda arm demonstrated statistically significant improvements in the EFS, co-primary endpoint, compared to the chemotherapy arm during the fourth interim analysis. At a median follow-up of 39 months, Keytruda arm demonstrated a 37% risk reduction in EFS events (including disease progression, recurrence, second primary cancer, or death from any cause) compared to chemotherapy arm (p=0.00031).
The other primary endpoint of pCR was achieved (63% vs. 56%) during the first interim analysis. Follow-up for OS is ongoing.
Additionally, based on the confirmatory data from KEYNOTE-522, the accelerated approval of Keytruda + chemotherapy was converted to full approval for PD-L1+ (CPS ≥10), 1L TNBC as determined by an FDA-approved test. The accelerated approval, granted in November 2020, was based on the Phase 3 KEYNOTE-355 study.
Implications: The approval marks the first immunotherapy combination approved in this patient segment. The application was reviewed based on RTOR and Assessment Aid to accelerate the process and approval was granted 5 months ahead of the PDUFA.
The review saw months of delays by the FDA. In February, FDA deferred the regulatory decision which resulted in a CRL in March due to unavailability of mature EFS data.
Although, Keytruda has the first mover advantage, Roche’s Tecentriq is next in line with similar trial design. SVB Leerink analyst predict US sales of $300-500 million in early stage TNBC for checkpoint inhibitors.

European Commission Approves Opdivo as Adjuvant Treatment for Esophageal or GEJ Cancer Patients with Residual Pathologic Disease Following Chemoradiotherapy
“We have demonstrated that the use of immunotherapy in earlier stages of cancer has the potential to prevent recurrence for certain patients,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb. “BMS was the first company to bring checkpoint inhibitors into the adjuvant setting for the treatment of patients with melanoma, and we are pleased to be the first to bring adjuvant therapy to patients in the EU with esophageal or gastroesophageal junction cancers who continue to face a high unmet need.”

ERYTECH Granted U.S. FDA Fast Track Designation for Eryaspase in Hypersensitive ALL
“This is yet another significant milestone and meaningful inflection point in advancing our lead product candidate eryaspase, further supporting our recently announced intention to submit a BLA for eryaspase in hypersensitive ALL patients,” said Gil Beyen, CEO of ERYTECH. “We believe that the FDA’s Fast Track designation for eryaspase underscores its potential to address this high unmet medical need.”

First Patient with Advanced HER2-Positive Breast Cancer Dosed with Zanidatamab + Tukysa® (Tucatinib) and Chemotherapy
“Recent clinical trials have demonstrated the benefit of combining tucatinib with trastuzumab and chemotherapy in patients with metastatic HER2-positive breast cancer,” said Neil Josephson, M.D., Interim Chief Medical Officer at Zymeworks. “Given the antitumor activity of zanidatamab observed across a range of HER2-overexpressing tumors and preclinical studies demonstrating improved anti-tumor activity of zanidatamab compared to trastuzumab, we believe the combination of zanidatamab with tucatinib and chemotherapy has the potential to be an impactful treatment for patients with advanced HER2-positive breast cancer, including those with brain metastases.” Josephson added, “this new study cohort complements our ongoing trials with zanidatamab in combination with other standard of care treatment regimens and supports our goal of establishing zanidatamab as the foundational therapy for HER2‑expressing cancers.”

Skewed rate of immunization revealed the role of ethnicity and racial disparity in preventable deaths
A lower vaccination rate in the racial and ethnically minor populations is causing adults to succumb to preventable deaths, a recent study published in the American Journal of Preventive Medicine suggests. A staggering range of 12,000 to 61,000 adults die from influenza alone. According to the study authors Kosuke Kawai, ScD, and Alison Tse Kawai, ScD: “Unfortunately, as we observed for vaccines against influenza, pneumococcal, shingles, and Tdap, a combination vaccine that protects against tetanus, diphtheria, and pertussis, adults from racial and ethnic minorities have had lower rates of COVID-19 vaccine uptake.”
Using data analytics between 2010 to 2019, the study examined vaccination trends factoring in race/ethnicity/socioeconomic conditions towards vaccination and used the data source of National Health Interview Surveys (NHIS). Vaccine coverage was studied for the following diseases: influenza, pneumococcal disease, herpes zoster, and Tdap. Collected data represented demographics, health status, insurance coverage, healthcare access, and health behaviors from a nationally representative sample. All these factors were found to influence the decision of the subjects to get vaccinated or not. Interestingly, Affordable Care Act was able to marginally improve the disparity between the age group of 18-64, although people from 65 to above were showed no difference. Black and Latino populations were found to have lower rates of immunization compared to the whites.